Breast cancer is one of the most reported cancers that can lead to death. Despite the advances in diagnosis and treatment procedures, the possibility of cancer recurrences is still high in many cases. With that in consideration, researchers from all over the world are showing interest in the unique features of Graphene oxide (GO), such as its excellent and versatile physicochemical properties, to explore further its potential and benefits towards breast cancer cell treatment. In this study, the cell viability and electrical response of GO, in terms of resistivity and impedance towards the breast cancer cells (MCF7) and normal breast cells (MCF10a), were investigated by varying the pH and concentration of GO. Firstly, the numbers of MCF7 and MCF10a were measured after being treated with GO for 24 and 48 h. Next, the electrical responses of these cells were evaluated by using interdigitated gold electrodes (IDEs) that are connected to an LCR meter. Based on the results obtained, as the pH of GO increased from pH 5 to pH 7, the number of viable MCF7 cells decreased while the number of viable MCF10a slightly increased after the incubation period of 48 h. Similarly, the MCF7 also experienced higher cytotoxicity effects when treated with GO concentrations of more than 25 μg/mL. The findings from the electrical characterization of the cells observed that the number of viable cells has corresponded to the impedance of the cells. The electrical impedance of MCF7 decreased as the number of highly insulating viable cell membranes decreased. But in contrast, the electrical impedance of MCF10a increased as the number of highly insulating viable cell membranes increased. Hence, it can be deduced that the GO with higher pH and concentration influence the MCF7 cancer cell line and MCF10a normal breast cell.
- MeSH
- apoptóza účinky léků MeSH
- elektrická impedance terapeutické užití MeSH
- elektrody MeSH
- grafit farmakologie MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- MFC-7 buňky MeSH
- nádorové buněčné linie MeSH
- nádory prsu farmakoterapie MeSH
- počet buněk MeSH
- prsy účinky léků MeSH
- viabilita buněk účinky léků MeSH
- zlato farmakologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The tumor suppressor p53 plays a key role in malignant transformation and tumor development. However, the frequency of p53 mutations within individual types of cancer is different, suggesting the existence of other mechanisms attenuating p53 tumor suppressor activity. Changes in upstream regulators of p53 such as MDM2 amplification and overexpression, expression of viral oncoproteins, estrogen receptor signaling, or changes in p53 transcriptional target genes were previously described in wild-type p53 tumors. We identified a novel pathway responsible for attenuation of p53 activity in human cancers. We demonstrate that AGR2, which is overexpressed in a variety of human cancers and provides a poor prognosis, up-regulates DUSP10 which subsequently inhibits p38 MAPK and prevents p53 activation by phosphorylation. Analysis of human breast cancers reveals that AGR2 specifically provides a poor prognosis in ER+ breast cancers with wild-type p53 but not ER- or mutant p53 breast cancers, and analysis of independent data sets show that DUSP10 levels also have prognostic significance in this specific sub-group of patients. These data not only reveal a novel pro-oncogenic signaling pathway mediating resistance to DNA damaging agents in human tumors, but also has implications for designing alternative strategies for modulation of wild-type p53 activity in cancer therapy.
- MeSH
- aktivace enzymů účinky léků MeSH
- antitumorózní látky farmakologie MeSH
- chemorezistence MeSH
- dospělí MeSH
- fosfatasy MAP kinas metabolismus MeSH
- fosfatasy s dvojí specifitou metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitogenem aktivované proteinkinasy p38 metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- nádory prsu farmakoterapie metabolismus patologie MeSH
- nádory farmakoterapie metabolismus patologie MeSH
- proteiny metabolismus MeSH
- prsy účinky léků metabolismus patologie MeSH
- senioři MeSH
- signální transdukce * účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Cells of the tumor microenvironment are recognized as important determinants of the tumor biology. The adjacent non-malignant cells can regulate drug responses of the cancer cells by secreted paracrine factors and direct interactions with tumor cells. RESULTS: Human mesenchymal stromal cells (MSC) actively contribute to tumor microenvironment. Here we focused on their response to chemotherapy as during the treatment these cells become affected. We have shown that the secretory phenotype and behavior of mesenchymal stromal cells influenced by cisplatin differs from the naïve MSC. MSC were more resistant to the concentrations of cisplatin, which was cytotoxic for tumor cells. They did not undergo apoptosis, but a part of MSC population underwent senescence. However, MSC pretreatment with cisplatin led to changes in phosphorylation profiles of many kinases and also increased secretion of IL-6 and IL-8 cytokines. These changes in cytokine and phosphorylation profile of MSC led to increased chemoresistance and stemness of breast cancer cells. CONCLUSION: Taken together here we suggest that the exposure of the chemoresistant cells in the tumor microenvironment leads to substantial alterations and might lead to promotion of acquired microenvironment-mediated chemoresistance and stemness.
- MeSH
- antitumorózní látky farmakologie MeSH
- apoptóza účinky léků MeSH
- chemorezistence MeSH
- cisplatina farmakologie MeSH
- interleukin-6 imunologie MeSH
- interleukin-8 imunologie MeSH
- lidé MeSH
- mezenchymální kmenové buňky cytologie účinky léků imunologie MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí účinky léků MeSH
- nádory prsu farmakoterapie imunologie MeSH
- prsy účinky léků imunologie MeSH
- stárnutí buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G2/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms.
- MeSH
- genistein chemie farmakologie terapeutické užití MeSH
- Glycine max chemie MeSH
- inhibitory angiogeneze chemie farmakologie terapeutické užití MeSH
- isoflavony chemie farmakologie terapeutické užití MeSH
- lidé MeSH
- nádory prsu krevní zásobení farmakoterapie metabolismus patologie MeSH
- patologická angiogeneze farmakoterapie metabolismus patologie MeSH
- prsy krevní zásobení účinky léků metabolismus patologie MeSH
- signální transdukce účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Klíčová slova
- Phytosoya,
- MeSH
- endometrium účinky léků MeSH
- fytoterapie metody MeSH
- Glycine max MeSH
- lidé středního věku MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- postmenopauza účinky léků MeSH
- prospektivní studie MeSH
- prsy účinky léků MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
The resistance to interferons (IFNs) limits their anticancer therapeutic efficacy. Here we studied the antiproliferative effect of interferon gamma in relation to SOCS3 expression in a panel of breast cancer cell lines and normal mammary epithelial cells. Compared to normal cells most breast cancer lines (7/8) were highly resistant to IFN-gamma. Using Northern blot and real time RT-PCR we investigated transcription of SOCS3 genes. All normal epithelial cells (4/4) showed SOCS3 induction (2-14 fold) while most breast cancer lines did not or weakly activated SOCS3 after the interferon gamma treatment. Among the cancer lines, the MDA-MB-468 cells showed increased sensitivity to IFN-gamma and relatively high level of SOCS3 induction (2-3 fold). Together, there was a good correlation
- MeSH
- chemorezistence MeSH
- fosforylace MeSH
- interferon gama farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prsu farmakoterapie metabolismus patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- proteiny SOCS genetika MeSH
- prsy metabolismus účinky léků MeSH
- transkripční faktor STAT1 metabolismus MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- MeSH
- antagonisté androgenů terapeutické užití MeSH
- deprese etiologie MeSH
- estradiol aplikace a dávkování škodlivé účinky MeSH
- hypofýza účinky léků MeSH
- kosti a kostní tkáň účinky léků MeSH
- lidé MeSH
- mozek účinky léků MeSH
- pohlavní steroidní hormony škodlivé účinky terapeutické užití MeSH
- poskytování zdravotní péče MeSH
- progestiny terapeutické užití MeSH
- prsy účinky léků MeSH
- testosteron aplikace a dávkování škodlivé účinky MeSH
- transsexualismus diagnóza farmakoterapie psychologie MeSH
- tromboembolie chemicky indukované MeSH
- vlasový folikul účinky léků MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- souhrny MeSH
